The U.S. Food & Drug Administration (FDA) just warned that Samsca (tolvaptan), manufactured by Otsuka America Pharmaceutical, has been linked to serious liver injury in a clinical trial of the drug.
Samsca is a selective vasopressin V2-receptor antagonist approved for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. These are electrolyte disorders in which there is an imbalance in the sodium and water levels in the body. These metabolic conditions, explained PubMedHealth, can lead to a broad array of adverse health reactions.
Samsca was recently tested in a clinical trial with patients diagnosed with autosomal dominant polycystic kidney disease (ADPKD), a genetic disorder in which many cysts form in the kidneys, causing the kidneys to become enlarged. Samsca is not FDA-approved for the treatment of ADPKD.
During the clinical trial, three cases of serious increases in hepatic (liver) enzymes were seen, said MedPage Today. According to the “Dear Healthcare Provider” warning letter sent to physicians, Otsuka said that, “An external panel of liver experts assessed these three cases as being either probably or highly likely to be caused by tolvaptan. These findings indicate that Samsca (tolvaptan) has the potential to cause irreversible and potentially fatal liver injury,”
The increase was seen in 22 of the 1,400 participants of the three-year, double-blind, placebo-controlled trial. One liver enzyme (serum alanine aminotransferase—ALT) was found to be three times greater than the upper limit of normal in this group, said MedPage Today. These participants also had elevated levels of another enzyme (serum total bilirubin) at levels two times greater than the upper limit of normal.
Although Otsuka stated that, “the elevations gradually improved after discontinuation of tolvaptan,” it and the FDA found that the liver injury risks seen in this trial could potentially be seen in other patients, said MedPage Today.
And, although the drug maker said that elevated liver enzymes were not seen in clinical trials for hyponatremia, it did acknowledge that, “these data are not adequate to exclude the possibility that patients receiving Samsca for its indicated use of clinically significant hypervolemic and euvolemic hyponatremia are at a potentially increased risk for irreversible and possibly fatal liver injury.”
In fact, the drug maker said that patients taking Samsca and who have underlying liver disease that may cause or contribute to hyponatremia may be less able to recover from drug-induced liver injury, suggesting that “Limiting the duration of Samsca therapy may reduce the risk of developing liver injury,” according to MedPage Today.
Otsuka recommended healthcare providers order liver tests in their patients with symptoms that are consistent with hepatic (liver) injury:
· Discomfort in the upper, right abdomen
· Dark urine
“If hepatic injury is suspected, Samsca should be promptly discontinued, appropriate treatment should be instituted, and investigations should be performed to determine probable cause,” Otsuka said, wrote MedPage Today. “Samsca should not be re-initiated in patients unless the cause for the observed liver injury is definitively established to be unrelated to treatment with Samsca.”
Most of the liver enzyme abnormalities were observed during the first 18 months of therapy.